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Genetic Research and Mouse Models Uncover Causes of Autoimmunity

Ever since the 1950s – when James Watson, Francis Crick, Rosalind Franklin, and other pertinent scientists uncovered the structure of deoxyribose nucleic acids (DNA) – the field of genetics has erupted and played a significant role in scientific research.

More recently, scientists from the National Institutes of Health have uncovered that a gene called BACH2 may be responsible for a variety of allergic and autoimmune conditions. The diseases BACH2 may play a role in include asthma, multiple sclerosis, Crohn’s disease, type-1 diabetes, and celiac disease.

Autoimmune diseases essentially occur when the immune system harms normal, healthy cells and tissues in the human body. Normally, these cells should not trigger immune responses, but autoimmunity has often occurred in infectious diseases and cancer.

Based on past research that shows mutations in the BACH2 gene leads to allergic reactions and a compromised immune system, the scientists from NIH used a mouse model to analyze how the BACH2 gene regulated immune response. The paper developed by scientists from the National Cancer Institute (NCI) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) was published online in Nature during the summer of 2013.

The discovery that the BACH2 gene is critical to regulating the immune system’s reactions is vital for the scientific community and may help further the development of therapies for autoimmune disorders. Genome-wide association studies were crucial for this specific finding, as such analytics discover whether certain genetic variants are linked with specific traits. The trait in this case is an overactive immune system.

Genome-wide association studies show that the DNA of various patients with autoimmune disorders have at least minor changes in the BACH2 gene, which triggered this mouse model preclinical trial.

“What was exciting was the opportunity to apply cutting-edge technology permitted by the completion of the Human Genome Project,” NIAMS scientific director Dr. John O’Shea, told the NIH reporter. “Using genome-wide approaches we were able to map the action of BACH2 across all genes. This enabled us to gain a clearer understanding of BACH2’s key role in the immune system.”

A healthy immune system works with the help of CD4+T cells, which activate immune response, and regulatory T cells, which restrict immune response. If CD4+T cells act aggressively, excessive tissue inflammation results, which is a key symptom of autoimmune diseases. This may bring about tissue and organ damage, which is a serious and sometimes fatal issue.

The researchers found that the BACH2 gene was significantly relevant for managing the stability between inflammatory and regulatory cells in the animal models. When the gene was missing or mutated, the CD4+T cells would become inflammatory. In fact, the mice died after a few months of life. However, when the BACH2 gene was reinstalled with the help of gene therapy, the mice were once again able to produce regulatory cells.

This type of research illustrates the importance of incorporating animal models of human disease in preclinical trials. With the utilization of mouse models, scientists may come much closer to developing superior therapies for autoimmune diseases.